4-methyl-3-oxopentanoic acid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl isobutyrylacetate (20.47 g, 129 mmol) and 1.5 M aq NaOH (250 mL) is stirred at room temperature overnight. The solution is then cooled to 0° C. and acidified to pH 1-2 by the slow addition of conc. HCl (˜35 mL). The solution is then saturated with NaCl and extracted thrice with EtOAc and once with CHCl3. The combined extracts are dried over Na2SO4 and concentrated to 14.46 g (86%) of isobutyrylacetic acid as an oil. 1H NMR (CDCl3, 300 MHz) reveals a mixture of keto and enol forms (˜4:1), in favor of the keto form. Keto form: δ 3.57 (s, 2H), 2.73 (sept, J=6.9 Hz, 1H), 1.16 (d, J=6.9 Hz, 6H) ppm. Enol form: 11.85 (s, 1H), 5.03 (s, 1H), 2.44 (sept, J=6.9 Hz, 1H), 1.10 (d, J=6.9 Hz, 6H) ppm. The solution is then cooled to 0° C. saturated with NaCl and extracted thrice with EtOAc The combined extracts are dried over Na2SO4 concentrated to 14.46 g (86%) of isobutyrylacetic acid as an oil a mixture of keto and enol forms (˜4:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl isobutyrylacetate (20.47 g, 129 mmol) and 1.5 M aq NaOH (250 mL) is stirred at room temperature overnight. The solution is then cooled to 0° C. and acidified to pH 1-2 by the slow addition of conc. HCl (˜35 mL). The solution is then saturated with NaCl and extracted thrice with EtOAc and once with CHCl3. The combined extracts are dried over Na2SO4 and concentrated to 14.46 g (86%) of isobutyrylacetic acid as an oil. 1H NMR (CDCl3, 300 MHz) reveals a mixture of keto and enol forms (˜4:1), in favor of the keto form. Keto form: δ 3.57 (s, 2H), 2.73 (sept, J=6.9 Hz, 1H), 1.16 (d, J=6.9 Hz, 6H) ppm. Enol form: 11.85 (s, 1H), 5.03 (s, 1H), 2.44 (sept, J=6.9 Hz, 1H), 1.10 (d, J=6.9 Hz, 6H) ppm. The solution is then cooled to 0° C. saturated with NaCl and extracted thrice with EtOAc The combined extracts are dried over Na2SO4 concentrated to 14.46 g (86%) of isobutyrylacetic acid as an oil a mixture of keto and enol forms (˜4:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Methyl-3-oxo-pentanoic acid (16.4 g, 126 mmol) was taken up in THF (200 mL) at room temperature under a nitrogen atmosphere, and 1,1-carbonyldiimidazole (22.4 g, 138 mmol) was added in one portion. The reuslting yellow solution was stirred at room temperature for 16 h, and then concentrated in vacuo and the residue diluted with DCM (200 mL). The solution was washed with 2N HCl (100 mL) and water (100 mL) and the aqueous was re-extracted with DCM (50 mL). The combined organics were dried over sodium sulfate and were then concentrated in vacuo to give the title compound as a yellow oil (11.7 g, 80%). concentrated in vacuo the residue diluted with DCM (200 mL) The solution was washed with 2N HCl (100 mL) and water (100 mL) the aqueous was re-extracted with DCM (50 mL) The combined organics were dried over sodium sulfate were then concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Methyl-3-oxo-pentanoic acid (16.4 g, 126 mmol) was taken up in THF (200 mL) at room temperature under a nitrogen atmosphere, and 1,1-carbonyldiimidazole (22.4 g, 138 mmol) was added in one portion. The reuslting yellow solution was stirred at room temperature for 16 h, and then concentrated in vacuo and the residue diluted with DCM (200 mL). The solution was washed with 2N HCl (100 mL) and water (100 mL) and the aqueous was re-extracted with DCM (50 mL). The combined organics were dried over sodium sulfate and were then concentrated in vacuo to give the title compound as a yellow oil (11.7 g, 80%). concentrated in vacuo the residue diluted with DCM (200 mL) The solution was washed with 2N HCl (100 mL) and water (100 mL) the aqueous was re-extracted with DCM (50 mL) The combined organics were dried over sodium sulfate were then concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl isobutyrylacetic acid (21 g, 132 mmol) was taken up in a 1.5M sodium hydroxide solution (15 g in 250 mL water) and stirred at room temperature over 16 h. The solution was cooled to 0° C. in an ice bath and was then acidified with 35 mL conc. Hydrochloric acid to pH 1-2. The resulting solution was saturated with sodium chloride and was then extracted with ethyl acetate (3×300 mL). The combined extracts were dried over sodium sulfate and then filtered and concentrated in vacuo to give the title compound as a clear oil (16.4 g, 95%). The solution was cooled to 0° C. in an ice bath was then extracted with ethyl acetate (3×300 mL) The combined extracts were dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diethanolamine (0.33 g) was dissolved in water (5 ml) and an ether solution (10 ml) containing the isobutyrylacetic acid (0.43 g) was added thereto. Next, while stirring the obtained mixture at 15° C., an aqueous solution (5 ml) containing silver nitrate (0.51 g) was added dropwise thereto and further stirred for 15 minutes. The precipitated white precipitate was filtered out, thereby obtaining silver isobutyrylacetate (yield: 0.37 g). was added was added dropwise further stirred for 15 minutes The precipitated white precipitate was filtered out

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydroxide (0.4 g) was dissolved in water (10 ml) and methyl isobutyrylacetate (manufactured by Fluka Corp., 1.44 g) was added thereto and stirred for 6 hours at room temperature. The reaction product was washed with ether and ether extraction was performed by adding a 10%-dilute sulfuric acid (4.9 g). An excess of anhydrous sodium sulfate was added to the ether extract, drying was performed thereon, and the anhydrous sodium sulfate was removed by filtering. In addition, the ether was removed using a rotary evaporator and an isobutyrylacetic acid was obtained (yield: 1 g). The reaction product was washed with ether and ether extraction by adding a 10%-dilute sulfuric acid (4.9 g) An excess of anhydrous sodium sulfate was added to the ether extract drying the anhydrous sodium sulfate was removed by filtering In addition, the ether was removed a rotary evaporator

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydroxide (0.4 g) was dissolved in water (10 ml) and methyl isobutyrylacetate (manufactured by Fluka Corp., 1.44 g) was added thereto and stirred for 6 hours at room temperature. The reaction product was washed with ether and ether extraction was performed by adding a 10%-dilute sulfuric acid (4.9 g). An excess of anhydrous sodium sulfate was added to the ether extract, drying was performed thereon, and the anhydrous sodium sulfate was removed by filtering. In addition, the ether was removed using a rotary evaporator and an isobutyrylacetic acid was obtained (yield: 1 g). The reaction product was washed with ether and ether extraction by adding a 10%-dilute sulfuric acid (4.9 g) An excess of anhydrous sodium sulfate was added to the ether extract drying the anhydrous sodium sulfate was removed by filtering In addition, the ether was removed a rotary evaporator

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diethanolamine (0.33 g) was dissolved in water (5 mL), and to this was added an ether solution (10 mL) containing isobutyrylacetic acid (0.43 g). Next, the mixture was stirred at 15° C. while an aqueous solution (5 mL) containing silver nitrate (0.51 g) was added dropwise, and this further was stirred for 15 minutes. The white precipitate that settled was filtered off to obtain silver isobutyrylacetate (yield 0.37 g). FIG. 1 shows the infrared absorption spectrum (IR) of the silver isobutyrylacetate that was obtained. IR:1709 cm−1, 1505 cm−1. was added dropwise The white precipitate that settled was filtered off

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diethanolamine (0.33 g) was dissolved in water (5 mL), and to this was added an ether solution (10 mL) containing isobutyrylacetic acid (0.43 g). Next, the mixture was stirred at 15° C. while an aqueous solution (5 mL) containing silver nitrate (0.51 g) was added dropwise, and this further was stirred for 15 minutes. The white precipitate that settled was filtered off to obtain silver isobutyrylacetate (yield 0.37 g). FIG. 1 shows the infrared absorption spectrum (IR) of the silver isobutyrylacetate that was obtained. IR:1709 cm−1, 1505 cm−1. was added dropwise The white precipitate that settled was filtered off

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diethanolamine (0.33 g) was dissolved in water (5 mL), and to this was added an ether solution (10 mL) containing isobutyrylacetic acid (0.43 g). Next, the mixture was stirred at 15° C. while an aqueous solution (5 mL) containing silver nitrate (0.51 g) was added dropwise, and this further was stirred for 15 minutes. The white precipitate that settled was filtered off to obtain silver isobutyrylacetate (yield 0.37 g). FIG. 1 shows the infrared absorption spectrum (IR) of the silver isobutyrylacetate that was obtained. IR:1709 cm−1, 1505 cm−1. was added dropwise The white precipitate that settled was filtered off

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydroxide (0.4 g) was dissolved in water (10 mL), and methyl isobutyrylacetate (1.44 g: made by Fluka) was added and this was agitated for six hours at room temperature. The reaction product was washed with ether, then 10% dilute sulfuric acid (4.9 g) was added and the mixture was extracted with ether. The ether extract was dried by adding excess anhydrous sodium sulfate, and the anhydrous sodium sulfate was removed by filtration. The ether was then removed with a rotary evaporator, yielding isobutyrylacetic acid (yield 1 g). The reaction product was washed with ether 10% dilute sulfuric acid (4.9 g) was added the mixture was extracted with ether The ether extract was dried by adding excess anhydrous sodium sulfate the anhydrous sodium sulfate was removed by filtration The ether was then removed with a rotary evaporator